Differential modulation of synaptic plasticity and local circuit activity in the dentate gyrus and CA1 regions of the rat hippocampus by corticosterone

Abstract

Depending on its severity, timing and context, stress has been shown to have a differential regional effect on hippocampal synaptic plasticity. While the focus of attention in most recent studies is on excitatory synapses and generation, modifications of inhibitory synapses and local interneurons cannot be ignored. We have now examined the effects of corticosterone (CORT) on extrinsic afferent and local circuit plasticity of the perforant path on the dentate gyrus (DG) and the ventral hippocampal commissure on CA1. Local circuit activity was measured by responses to paired-pulse stimulation. Control rats expressed afferent long-term potentiation (LTP) and local circuit plasticity in both the DG and CA1. Administration of a high dosage of CORT-reduced paired-pulse inhibition and increased facilitation in DG but not in CA1, whereas administration of a moderate CORT dosage had no effect. Moderate CORT doses caused enhancement of LTP in the DG but not in CA1, while high CORT doses converted LTP to long-term depression in the CA1 but had no effect in the DG. CORT blocked theta burst stimulation-induced local circuit plasticity otherwise found in control DG. These findings suggest that elevation of the level of CORT results in a regionally differentiated physiological response. In addition, the results indicate that CORT affects aspects of local circuit activity and plasticity in the DG but less so in the CA1. It is possible that these differentiated alterations underlie some of the behavioral consequences and memory processes under stressful conditions.